Medical images are images of a human subject that are analyzed for the purposes of diagnosing and treating disease, injury and birth defects. While medical images may be captured using conventional photography, more commonly, medical images involve modalities that are able to image the internal structure of the subject in a non-invasive manner. Examples of such modalities include computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), ultrasound, fluoroscopy, conventional x-rays, and the like. Medical images may be analog or digital, two-dimensional or three-dimensional; however, three-dimensional modalities are digital.
The term “bone” may be used to refer to various levels of bone structure, composition and organization, from the gross visual, naked eye identification of a specific whole bone or a part of a whole bone such as the femur (the upper bone of the thigh), viz., “bone” as an organ or a part of an organ, to the specific structural organization of portions of a bone by light microscopy, that is, of “bone” as a tissue, e.g., compact bone (cortex or hard shell) or cancellous (spongy or trabecular) bone, or even to the organization of the individual components of bone tissue, that is, “bone” as a substance or material (bone substance) whose individual components can be visualized, for example, by electron microscopy and other techniques.
The basic bone substance or material is composed principally of a soft matrix consisting primarily of the (fibrous) protein collagen and small amounts of other organic constituents and other extracellular, extravascular organic constituents and is referred to as the organic matrix of bone substance. It is into this matrix that the other major component of bone substance, the hard crystals of calcium-phosphate (“apatite”) (solid mineral phase), is deposited. Therefore, the two major components of bone substance are: (1) a soft organic matrix (hereinafter also referred to as spongy or trabecular) and (2) the hard solid phase of the calcium-phosphate crystals, the solid mineral phase (hereinafter also referred to as cortex or hard shell). These two components provide a good portion of the mechanical properties of bone as an organ, a tissue and a material substance, as well as many of the physiological functions of bone substance. The organic matrix of bone substance is ordinarily considered to consist of the extracellular, extravascular organic components of the bone substance and the bone tissue, and is chemically analyzed by measuring the collagen or collagen and other known proteins and organic constituents of the extracellular, extravascular matrix.
There are 5 types of bone found within the human body. These are long bones, short bones, flat bones, irregular bones and sesamoid bones.
Long bones are some of the longest bones in the body, such as the Femur, Humerus and Tibia but are also some of the smallest including the Metacarpals, Metatarsals and Phalanges. The classification of a long bone includes having a body which is longer than it is wide, with growth plates (epiphysis) at either end, having a hard outer surface of compact bone and a spongy inner known an cancellous bone containing bone marrow. Both ends of the bone are covered in hyaline cartilage to help protect the bone and aid shock absorbtion.
Short bones are defined as being approximately as wide as they are long and have a primary function of providing support and stability with little movement. Examples of short bones are the Carpals and Tarsals in the wrist and foot. They consist of only a thin layer of compact, hard bone with cancellous bone on the inside along with relatively large amounts of bone marrow.
Flat bones are as they sound, strong, flat plates of bone with the main function of providing protection to the bodies vital organs and being a base for muscular attachment. The classic example of a flat bone is the Scapula (shoulder blade). The Sternum (breast bone), Cranium (skull), Pelvis and Ribs are also classified as flat bones. Anterior and posterior surfaces are formed of compact bone to provide strength for protection with the center consisting of cancellous (spongy) bone and varying amounts of bone marrow. In adults, the highest number of red blood cells are formed in flat bones.
Irregular bones are bones which do not fall into any other category due to their non-uniform shape. Good examples of these are the Vertebrae, Sacrum and Mandible (lower jaw). They primarily consist of cancellous bone, with a thin outer layer of compact bone.
Sesamoid bones are usually short or irregular bones, imbedded in a tendon. The most obvious example of this is the Patella (knee cap) which sits within the Patella or Quadriceps tendon. Other sesamoid bones are the Pisiform (smallest of the Carpals) and the two small bones at the base of the 1st Metatarsal. Sesamoid bones are usually present in a tendon where it passes over a joint which serves to protect the tendon.
Techniques for measuring bone mineral density non-invasively have been developed. Two such techniques are by X-ray and by magnetic resonance imaging (MRI).
Currently, two of the most commonly used techniques to measure bone mineral density are: (1) dual energy x-ray absorptiometry (DXA) and (2) computed tomography (CT). DXA utilizes x-rays of two energies. The mineral and soft tissue each exhibit different x-ray scattering cross sections at each energy level, enabling a map of mineral density to be computed from the scan data. However, because of the variable composition of the soft tissue and its variable depth along the view direction, overlapping bone structure and the inhomogeneity of the 3-D spatial distribution of the trabeculae in cancellous bone, for example, the most commonly analyzed bone tissue using this technique, the 2-D (areal) measurement of bone mineral density may not reflect the true volumetric 3-D bone mineral density. Indeed, serious questions have been raised in the literature about the validity and usefulness of the data obtained by DXA.
Computed tomography (CT) produces an accurate measurement of volumetric, 3-D bone mineral density (grams per cubic centimeter). However, when the x-ray intensity is sufficient to make the CT scan quantitatively accurate (quantitative CT or QCT), the radiation dose to the patient is high, limiting the number of scans permissible for a single patient, thus preventing the use of QCT on women of child bearing age, growing children and patients who may require repeated measurements in order to follow and assess the course of a disease or injury or to assess the efficacy of treatment. Like any x-ray based measurement, CT does not distinguish bone matrix from soft tissue, and CT is susceptible to errors because of the variability of soft tissue composition and depth.
Osteoporosis is characterized by low bone mass or bone mineral density, micro-architectural deterioration of the bone and increased fracture risks [1-2]. High-resolution peripheral quantitative computed tomography (HR-pQCT) (XtremeCT, Scanco Medical AG, Switzerland) is a newly available technology. Compared to the conventional technologies for diagnosis of osteoporosis using dual-energy X-ray absorptiometry (DXA), HR-pQCT not only measures the bone mineral density, but also provides structural parameters on the complex micro-architecture of the bone quantitatively. HR-pQCT has already found wide clinical applications in the evaluation of bone micro-architecture, therapeutic efficacy for treatment of osteoporosis, assessment of bone strength and prediction of fracture risk [3-10]. With the aid of computational technologies, i.e., surface extraction and three-dimensional (3-D) rendering, technicians are able to inspect both the cortex (the hard shell) and the trabecular (the spongy of bone) compartments of bone. In addition, the low radiation dosage (<5 μSv) of HR-pQCT warrants its safety in clinical applications [3].
For clinical applications, it is important to be able to accurately analyze bone changes in both density and structure, and longitudinally assess the bone quality, in particular the morphometric analysis of the bone micro-architecture in aging and under the influence of both pharmaceutical and non-pharmaceutical interventions. Therefore, an image analysis procedure with proper alignment of the bony structures in the volumetric data of the baseline and follow-up scans of HR-pQCT is crucial. The evaluation software embedded in the HR-pQCT scanner is able to provide detailed bone morphometric data [11] but the comparison among different scans is limited in the following aspects. The bone contours were identified using the semi-automatic slice-by-slice delineation, which is an inefficient and labor-intensive process. The common region was determined in the scanner as the slices with the same bone area between the two scans. Although the long cast provides support for the arm or leg and prevents the limb from being tilted, care needs to be taken in reposition of the limb in the same way into the cast, which is a manual process with limited precision. In fact, the follow-up scan is inevitably tilted to some extent compared to the baseline, and the anatomical meanings of the cross-sectional slices are not exactly identical. Consequently, the measurement of common region in that case will not be entirely reliable. Instead, if the pose difference between the two volumetric datasets could be explicitly determined, the problem of intra-subject image alignment will be solved. This is one of problems to be solved in this disclosure.
There exist several image registration software programs, such as Statistical Parametric Mapping (SPM) [12], FMRIB Software Library (FSL) [13], and Image Registration Toolkit [14]. In these software programs, the strategy is to apply registration on the overall image homogeneously without differentiating various tissue types. However, in the HR-pQCT images, the deformable non-skeletal structures such as muscles and soft tissues, and the rigid bony structures, should be treated differently. Besides, complexity in trabecular bone geometry and the large size of the HR-pQCT data also poses great challenges on the design of a clinically feasible registration algorithm. A comprehensive survey of existing approaches to the registration of micro-CT images can be found in [20], which compared three similarity measures used for image registration on a rat model. These image-based registration methods treat the bony and non-bone regions equally, so that the registration accuracy of bones was not optimal.
A tailor-made solution for accurate and efficient HR-pQCT volume registration is of special significance as it will allow flexible and comprehensive morphometric comparison in the longitudinal bone health studies being conducted in applicants' center and as reference for many other centers using HR-pQCT for clinical applications. In this disclosure, we propose a novel method to align the baseline and follow-up scans of the same subject with accuracy and efficiency. This method is featured in that no user interaction is needed throughout the whole process.